Butylglyceryl Pectin Nanoparticles: Synthesis, Formulation and Characterization

Abstract

Pectin is a polysaccharide with very good gel forming properties that traditionally has found important applications in foods and pharmaceutical industries. Although less studied, chemical modifications of pectin leading to a decrease in its hydrophilicity can be useful for the development of novel drug carriers. To this aim, butylglyceryl pectins (P-OX4) were synthesized via functionalization with n-butylglycidyl ether and subsequently formed into nanoparticles. Chromatographic, spectroscopic, and thermal analytical methods were employed to characterize the novel butylglyceryl pectins (P-OX4) obtained, prior to their formulation into nanoparticles via nanoprecipitation. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopy confirmed a degree of modification in these materials in the range 10.4–13.6%, and thermal stability studies indicated an increase in both the thermal decomposition onset and glass transition temperature values (compared to those of the original pectin). An increase in the molecular weight and a decrease in the viscosity of P-OX4, when compared to the starting material, were also observed. The resulting nanoformulations were investigated in terms of particle morphology, size and stability, and it was found that particles were roughly spherical, with their size below 300 nm, and a negative zeta potential (−20 to −26 mV, indicating good stability). Having demonstrated the ability to load Doxorubicin at the level of 10%, their potential in drug delivery applications warrants further investigations.

Investigations of amphiphilic butylglyceryl‐functionalized dextran nanoparticles for topical delivery

“…GPC technique was utilized to analyze the MW of DEX‐OX4 and an increase in the MW following modification was observed in the results (Table 2), hence supporting the previous results shown by NMR and FT‐IR analyses for successful modification—in accordance with the results shown in our previous study for butylglyceryl pectin 17 . The polymer polydispersity index (PDI) explains the molecular weight distribution of polymer chain, with values reported here ~1 suggesting a near‐monodispersed polymer chain distribution and homogenous branching.…”

“…The formula used to calculate DS for the functionalized dextran (DEX‐OX4) was derived from the integral of the peak ascribed to the end CH 3 group butyl chain ( δ 0.8 ppm) and the anomeric proton at C 1 (δ 4.9 ppm). An increase in the DS (~6.3%–35.7%) for lower molar ratio (1:1 and 1:5) used was illustrated in the results (Table 1), as opposed to our previous study synthesizing alkylated pectin with butylglycidyl ether in an aqueous alkali medium utilizing 1:19 molar ratio with DS values obtained ranged from 10% to 14% 17 . Conversely, higher DS values have been reported by Ibegbu et al in another alternative alkylation reaction of dextran in an organic medium with various alkyl chain lengths of alkylglycerols‐butyl, octyl, lauryl, or hexadecyl—at lower molar ratio (1:4) in the presence of potassium tert‐butoxide catalyst, with DS values that ranged from 68.5% to 144.9% 23 …”

“…The peak at 4.9 ppm was ascribed to the main anomeric proton (α‐1,6 linkages) and well separated from other backbone protons in the range 3.2–4 ppm 21,22 . The successful modification was affirmed by the presence of alkyl groups at 0.8, 1.3, and 1.5 ppm in the upfield region of the spectrum 17 …”

“…The bands appeared in the range 2926–2912 cm −1 can be ascribed to CH stretching vibrations. A comparison between FT‐IR spectrum of DEX‐OX4 with native dextran as illustrated in Figure 3b exemplified an increased in bands intensity at ~1077 and 1006 cm −1 (indicative of additional ether linkages COC formation) can be witnessed for butylglyceryl dextran 17,20 …”

“…Butylglyceryl‐functionalized dextran (DEX‐OX4) was synthesized by reacting native dextran with n ‐butylglycidyl ether (Figure 2) under a vigorous aqueous alkaline environment (NaOH, pH 14) via a nucleophilic substitution reaction, following a procedure described in the literature 17 . The substitution is expected to happen mainly at C 2 as the reactivity of hydroxyl groups follow the order C 2 > C 4 > C 3 18 .…”